MSD RESFLOR 250 ml VET ONLY (S4)

PHARMACOLOGICAL ACTION

Pharmacodynamics

Florfenicol is a semi-synthetic broad-spectrum antibiotic that is effective against most gram-positive and gram-negative bacteria isolated from domestic animals. Florfenicol acts by inhibiting bacterial protein synthesis at the ribosomal level. Laboratory tests have shown that florfenicol is effective against the most commonly isolated bacterial pathogens involved in bovine respiratory disease which include Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida, Histophilus somni and Trueperella pyogenes.

Florfenicol is considered to be a bacteriostatic agent, but in vitro studies of florfenicol demonstrate bactericidal activity against Mannheimia haemolytica, Pasteurella multocida and Histophilus somni.

Flunixin meglumine is a non-steroidal anti-inflammatory agent (NSAID) with analgesic and antipyretic activity. Flunixin meglumine acts as a reversible non-selective inhibitor of cyclo-oxygenase (both COX 1 and COX 2), an important enzyme in the arachidonic acid cascade pathway, which is responsible for converting arachidonic acid to cyclic endoperoxides. Consequently, synthesis of eicosanoids, important mediators of the inflammatory process involved in pyrexia, pain and tissue inflammation, is inhibited.

Through its effects on the arachidonic acid cascade, flunixin also inhibits the production of thromboxane, a potent platelet pro-aggregator and vasoconstrictor, which is released during blood clotting. Flunixin exerts its antipyretic effect by inhibiting prostaglandin E2 synthesis in the hypothalamus. Although flunixin has no direct effects on endotoxins after they have been produced, it reduces prostaglandin production and hence reduces the many effects of the prostaglandin cascade. Prostaglandins are part of the complex process involved in the development of endotoxic shock.

Pharmacokinetics

The administration of Resflor® by the subcutaneous route at the recommended dosage of 40 mg/kg florfenicol, maintained efficacious plasma levels in cattle (i.e., above the MIC90 of the least sensitive respiratory pathogen Mannheimia haemolytica) for longer than 39 hours. Maximum plasma concentration (Cmax) of approximately 4,3 μg/mℓ occurred approximately 5,5 hours (Tmax) after dosing.

After administration of Resflor® by the subcutaneous route at the recommended dosage of 2,2 mg/kg flunixin, peak plasma concentrations of 2,9 μg/mℓ were achieved after 1,3 hours. The apparent volume of distribution was approximately 2 ℓ/kg.

INDICATIONS

For use in cattle for clinical treatment of respiratory infections, caused by Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida and Histophilus somni associated with pyrexia.

CONTRAINDICATIONS

Do not use in adult bulls intended for breeding purposes.

Do not use in animals suffering from hepatic and renal diseases.

Do not use if there is a risk of gastrointestinal bleeding or in cases where there is evidence of altered haemostasis.

Do not use in lactating dairy cows.

Do not administer to animals less than 6 weeks of age.

WARNINGS

FOR VETERINARY USE ONLY.

The effect of florfenicol on bovine reproductive performance and pregnancy has not been assessed.

Withdrawal period: Meat and offal: 46 days

Milk: In the absence of a withdrawal time in respect of milk, do not use in cattle producing milk for human consumption.

The injection site volume of 10 mℓ must not be exceeded because of effects on residues.

DOSAGE AND DIRECTIONS FOR USE

Administer a single subcutaneous injection of 40 mg/kg florfenicol and 2,2 mg/kg flunixin (2 mℓ/15 kg body weight).

The injection should only be given in the neck.

Swab the rubber stopper before withdrawing each dose. Use a dry sterile needle and syringe.

Do not exceed the dose volume of 10 mℓ, given at any one injection site.

SIDE EFFECTS AND SPECIAL PRECAUTIONS

Avoid use in dehydrated, hypovolaemic or hypotensive animals, as there is a potential risk of increased renal toxicity.

Avoid concurrent administration of potentially nephrotoxic agents.

Subcutaneous administration of Resflor® may result in injection site swellings that become palpable 2 to 3 days after injection. The duration of the injection site swellings ranged from 15 to 36 days post injection. Grossly, this is associated with minimal to mild irritation of the subcutis. Extension into the underlying muscle was noted in only a few instances. By 56 days post-dosing, no lesions were observed that would require trimming at slaughter.

Special precautions to be taken by the person administering Resflor® to cattle

Do not use in known cases of sensitivity to propylene glycol and to polyethylene glycols.

Reproductive and developmental toxicities have been reported in laboratory animals following high, repeated exposures to N-methyl-2-pyrrolidone (NMP). Pregnant women should wear gloves and exercise caution or avoid handling Resflor®.

INTERACTIONS

Resflor® should not be administered to animals in conjunction with other NSAID’s or glucocorticosteroids.

Gastrointestinal tract ulceration may be exacerbated by corticosteroids in animals given NSAID’s.

Concurrent use of other active substances that have a high degree of protein binding, may compete with flunixin for binding and thus lead to toxic effects. Pre-treatment with other anti-inflammatory substances may result in additional or increased adverse effects, and

accordingly, a treatment-free period with such agents should be observed for at least 24 hours before the commencement of treatment. The treatment-free period however, should take into account the pharmacokinetic properties of the products used previously.

KNOWN SIGNS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT

Clinical signs include; decreased feed and water consumption and decreased body weight.

Tissue irritation increases with injection volume.

IDENTIFICATION

Clear, light yellow to straw coloured liquid, free from visible particles.

PRESENTATION

Type I, clear colourless glass vials of 100 mℓ and 250 mℓ, sealed with grey bromobutyl stoppers and aluminium seals. Each bottle is packed in a cardboard box.

STORAGE

Store at or below 25 °C.

After opening the bottle, use within 28 days.

KEEP OUT OF REACH AND SIGHT OF CHILDREN, UNINFORMED PERSONS AND ANIMALS.

REGISTRATION NUMBER

06/21.1/17 (Act 101/1965)

Namibia Reg. No. V14/17.1.10/1234 NS2

REGISTRATION HOLDER

Intervet South Africa (Pty) Ltd.

20 Spartan Road, Spartan

1619, RSA

Tel: +27 (0) 11 923 9300

E-mail: msdahza@msd.com

www.msd-animal-health.co.za

DATE OF NOTIFICATION OF APPROVAL OF THIS SCIENTIFIC PACKAGE INSERT

11 June 2024